LncRNA-Gm9866 promotes liver fibrosis by activating TGFβ/Smad signaling via targeting Fam98b

作者：Xiaomin Liao, Xianxian Ruan, Peishan Yao, Dan Yang, Xianbin Wu, Xia Zhou, Jing Jie, Dafu Wei, Yaodan Liang, Taicheng Zhang, Shanyu Qin, Haixing Jiang · 发表于：Journal of Translational Medicine · 年份：2023 · DOI：10.1186/s12967-023-04642-1 · 被引用次数：11 · 研究领域：Cancer-related molecular mechanisms research、Liver physiology and pathology、Connective Tissue Growth Factor Research

OBJECTIVE: The exact mechanism and target molecules of liver fibrosis have remained largely elusive. Here, we investigated the role of long noncoding RNA Gm9866(lncRNA-Gm9866) on liver fibrosis. METHODS: The transcription of lncRNA-Gm9866 in activated cells and mouse fibrotic livers was determined by quantitative polymerase chain reaction (qRT-PCR). The effects of lentivirus-mediated knockdown or overexpression of lncRNA-Gm9866 in liver fibrosis were examined in vitro and in vivo. Furthermore, bioinformatics analysis, cell samples validation, fluorescence in situ hybridization (FISH) co-localization, RNA binding protein immunoprecipitation (RIP), actinomycin D test and Western blot (WB) were carried out to explore the potential mechanism of lncRNA-Gm9866. RESULTS: The expression of α-smooth muscle actin (α-SMA), Collagen I (COL-1) and lncRNA-Gm9866 were significantly increased in tissues and cells. Overexpressing lncRNA-Gm9866 promoted the activation of hepatic stellate cells (HSCs). Silencing lncRNA-Gm9866 inhibited the activation of HSCs and transforming growth factor-β1 (TGFβ1) induced fibrosis. Overexpressing lncRNA-Gm9866 promoted hepatocytes (HCs) apoptosis and the expression of pro-fibrogenic genes, inhibited the proliferation and migration of HCs. Knockdown of lncRNA-Gm9866 inhibited the apoptosis of HCs, the expression of pro-fibrogenic genes, TGFβ1 induced fibrosis and the occurrence of carbon tetrachloride (CCl4)-induced liver fibrosis, and promoted the proliferati...